Propionic Acidemia (PCCB-Related) (PCCB)
Propionic acidemia (PCCB-related) is an autosomal recessive, pan-ethnic disease caused by pathogenic variants in the gene PCCB. Age of onset is usually infantile, but it may occur later in childhood or adolescence. In the infantile-onset disease, babies are born healthy but within several days they begin to vomit frequently and become lethargic. This metabolic crisis can lead to coma and death if not detected and treated, but even with treatment most babies develop brain damage. Metabolic crises are likely to occur during periods where the infant is sick or develops an infection. The later-onset form resembles the infantile form in many ways, but occurs after a period of relatively normal development. Symptoms of this form include developmental regression and cardiomyopathy. As patients with propionic aciduria grow, they may have intellectual disability and seizures, as well as cardiomyopathy and pancreatitis. Some patients also have vision and/or hearing loss. Most patients need to be fed by nasogastric tubes or gastrostomy. Null alleles and specific missense variants are associated with early-onset and severe disease, whereas other missense variants may retain some enzymatic function and result in a milder disease. Life expectancy is variable; for patients diagnosed before metabolic crisis, preventative treatment often results in a better outcome. Otherwise, life expectancy is limited and some patients die in childhood.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.